Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Study By UCSD Researchers Gives New Insight Into How Anthrax Bacteria Can Evade A Host’s Immune Response


Biologists at the University of California, San Diego have determined how toxin produced by anthrax bacteria blocks a person’s normal immune response, a discovery that could lead to new treatments for anthrax infection.

In a paper to be published in the January 15th issue of The Journal of Immunology the UCSD scientists show why, in the presence of anthrax toxin, human immune cells fail to respond normally to lipopolysaccharide—a component of the cell walls of many bacteria including the bacteria that cause anthrax, Bacillus anthracis. Bacterial invasion, or the presence of lipopolysaccharide, usually causes immune cells known as macrophages to release cytokines—chemicals that signal other cells about the presence of an invader. Release of cytokines causes large numbers of immune cells to arrive at the site of infection and destroy the bacteria. By blocking this host immune response, anthrax bacteria are able to multiply unchecked. According to the Centers for Disease Control, approximately 75 percent of people infected with inhalation anthrax die, even with all possible supportive care including appropriate antibiotics.

“Although it was known for quite some time that anthrax toxins can suppress cytokine production, the mechanism by which Bacillus anthracis escapes the immune response isn’t really understood,” says Michael David, a biology professor at UCSD who headed the research team. “We have identified a protein molecule targeted by the anthrax toxin and determined where it acts in the sequence of steps involved in immune response.”

Macrophages have special receptors on their surfaces that bind to lipopolysaccharide. The binding of lipopolysaccharide to this receptor sets off a sequence of events inside the macrophage, in which a series of proteins activate one another in turn. This cascade of proteins activating one another ultimately turns on cytokine genes, causing the macrophage to churn out large quantities of cytokines.

It turns out that there are two separate, sometimes cooperating, routes in the cell by which series of proteins activate one another to switch on production of cytokines. One of the routes has been recognized for a long time, but researchers were sometimes puzzled when cytokine production was turned on or off without the proteins along this route being activated or deactivated. This puzzle was resolved when the David group and other groups simultaneously identified the second route, the IRF3 pathway. The anthrax toxin targets the IRF3 pathway by cleaving MKK6—one of the proteins in the series along the route. The cleavage of MKK6 prevents the cytokine genes from being switched on.

When the researchers made mutant macrophages with a variant of MKK6 that could not be cleaved by the anthrax toxin, these macrophages responded to lipopolysaccharide by producing cytokines even in the presence of the anthrax toxin. This suggests that developing a drug that could protect MKK6 and prevent anthrax toxin from cleaving it could help to prevent an anthrax infection from getting out of control. The anthrax bacteria would be unable to evade the normal immune response.

“While these results may not lead to a drug to cure anthrax in the next six months, the more you understand about bacteria and how they target the immune response the more options you have for developing drugs to treat the infections,” says David.

Previous work by other researchers has suggested that anthrax toxin evades the immune system by killing macrophages; however, according to David, cell death does not fully explain how anthrax bacteria evade the immune system.

“Only some types of macrophages are killed by anthrax toxins, but anthrax toxins diminish the production of cytokines in all of the macrophages we have tested,” David explains. “Also, less toxin is needed to shut off the immune response than to kill the macrophages.”

The other UCSD researchers involved with this project were Oanh Dang, a former graduate student in the David laboratory and the first author of the paper; Lorena Navarro, a former graduate student in the David laboratory and first author on two other papers that initially identified the IRF3 immune response pathway; and Keith Anderson, a technician in the David laboratory. This work was supported by a grant from the National Institutes of Health.

Media Contacts: Sherry Seethaler (858) 534-4656
Comment: Michael David (858) 822-1108

Sherry Seethaler | UC - San Diego
Further information:

More articles from Life Sciences:

nachricht Make way for the mini flying machines
21.03.2018 | American Chemical Society

nachricht New 4-D printer could reshape the world we live in
21.03.2018 | American Chemical Society

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

New 4-D printer could reshape the world we live in

21.03.2018 | Life Sciences

Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

21.03.2018 | Trade Fair News

Physicists made crystal lattice from polaritons

20.03.2018 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>